ABSTRACT The University of Chicago Medicine Comprehensive Cancer Center (UCCCC) is submitting this competitive renewal application for its Cancer Center Support Grant for Years 43-47. The mission of the UCCCC is to elucidate the determinants of cancer, to develop cures for cancer, and to prevent cancer through research, clinical care, education, and community engagement. Our cancer research programs emphasize translational and transdisciplinary research, and we pursue this goal by promoting collaboration among a diverse and dedicated team of outstanding basic, translational, clinical, and population researchers. The 166 members of the UCCCC are organized into five established programs, all with a translational focus (Molecular Mechanisms of Cancer; Immunology and Cancer; Clinical and Experimental Therapeutics; Advanced Imaging; and Cancer Prevention and Control). Clinical research is a major focus of multidisciplinary activity at the UCCCC. The UCCCC has an extensive record in conducting all phases of clinical trials, and was awarded a U10 NCTN Lead Academic Participating Site (LAPS) award from the NCI. In addition, the UCCCC is a full member of the Alliance for Clinical Trials in Oncology, and the Children's Oncology Group (COG), and participates in NRG Oncology studies as a LAPS main member. In 2016, 914 individual patients were accrued to therapeutic protocols, with 383 accrued to investigator-initiated trials. In the period since the last review (2013-2016), the UCCCC contributed 2,121 peer-reviewed publications. Members are supported by $40.5 million (DC) in peer- reviewed funding, and $23.7 million in non-peer-reviewed funding. Funds are requested in this application for Program Leaders; Leadership, Planning and Evaluation; Developmental Funds, Administration, Clinical Protocol and Data Management; the Protocol Review and Monitoring System, Community Outreach and Engagement; Cancer Research Career Enhancement and Related Activities; and 10 shared resources (Bioinformatics, Biostatistics; Cytometry and Antibody Technology; Genomics; Human Immunologic Monitoring and cGMP; Human Tissue Resource Center; Integrated Microscopy; Integrated Small Animal Imaging Research Resource; Pharmacology; and Transgenic Mouse/Embryonic Stem Cell Facilities). Through an in-depth institutional review and multi-faceted strategic planning process, the UCCCC has new and strong institutional commitments, and a stable and experienced leadership team, and has developed and implemented a comprehensive strategic plan. Future development will focus on three major initiatives, which prioritize and accelerate laboratory, clinical and translational, and community-based cancer research: 1) developing new biomarkers, novel treatments, and new interventions to prevent cancer; 2) efficiently integrating effective treatments and interventions into medical practice; and 3) assessing the impact of these new approaches on health outcomes, and addressing cancers relevant to our catchment area. Underpinning each of these initiatives is computation-based models for cancer research and care.